Language and Risk for Schizophrenia

描述（由申请人提供）：这项R21提案是为了资助确定连接额叶和颞叶皮质的大脑白色物质通路的结构和功能变化是否在患有精神分裂症的遗传高风险人群中与低风险对照人群显着不同，并确定这些措施是否最终可以区分那些继续有症状的人与那些没有症状的人。因此，我们假设精神分裂症的神经发育基础是参与处理语言和相关功能的白色物质通路的紊乱，并且这些变化在具有发展疾病遗传风险的个体中比在没有遗传风险的个体中明显更好地被MRI检测到。为了检验这一假设，我们的目的是评估一个大的队列的个人（N=60）谁有一个增加的家族风险发展为精神分裂症，并比较他们的年龄，性别和社会阶层比例匹配的对照组（N=30）。将使用扩散张量成像协议（DTI）确定连接颞叶和额叶（钩状、弓形、下纵、下枕额束）区域中白色物质的完整性。上述大脑区域和通路异常激活的证据将通过功能磁共振成像直接征集，使用先前显示的词汇决策任务来区分精神分裂症患者和精神分裂症高危人群。结构变化与功能变化的相关性将提供对任何结构异常的意义的理解。由于相当多的个体在遗传风险队列中可能会在未来的某个时候发展为精神分裂症，在目前的研究中确定存在的缺陷可能会在以后被发现是高风险个体中可能发展为精神分裂症的生物标志物，因此对于早期干预的决策是有价值的。公共卫生相关性这是一项R21资金申请，旨在确定精神分裂症的遗传高危队列（N=60），并将其与脑额叶和颞叶白色物质通路完整性及其功能缺陷的低风险对照进行比较。MRI扫描将在2年内进行，以确定可用于未来研究的脑成像措施，以区分那些注定要发展精神分裂症的个体与那些在发病前没有发展精神分裂症的个体。

DESCRIPTION (provided by applicant): This R21 proposal is for funding to determine whether structural and functional changes in the brain white matter pathways that connect frontal and temporal cortices are significantly different in people who are at genetic high risk for developing schizophrenia compared with low risk controls and to determine whether these measures can eventually distinguish those who go on to have symptoms from those who do not. We thus hypothesize that the neurodevelopmental basis for schizophrenia is disturbance in the white matter pathways involved in processing language and related functions, and that these changes will be detectable by MRI in significantly more well individuals that are at genetic risk for developing the illness than in those who are not. In order to test this hypothesis, we aim to evaluate a large cohort of individuals (N=60) who have an increased familial risk for developing schizophrenia and compare them to an age, sex, and social class proportionally matched group of controls (N=30). The integrity of white matter in regions that connect the temporal and frontal lobes (uncinate, arcuate, inferior longitudinal, inferior occipito-frontal fasciculi) will be determined using a Diffusion Tensor Imaging Protocol (DTI). Evidence of anomalous activation within the above brain regions and pathways will be solicited directly by fMRI using a lexical decision task previously shown to differentiate people with schizophrenia and people at high-risk for schizophrenia from controls. The correlation of structural change with functional change will provide an understanding of the significance of any structural abnormalities. Since considerably more individuals in a genetically at risk cohort are likely to develop schizophrenia sometime in the future, the deficits determined to be present in this current study may be later found to be biological markers for whom among high-risk individuals are likely to develop schizophrenia and thus be valuable for decisions about early intervention. PUBLIC HEALTH RELEVANCE This is an R21 application for funding to ascertain a genetically at high-risk cohort for schizophrenia (N=60) and compare them to low-risk controls on deficits in the integrity of brain frontal and temporal lobe white matter pathways and their functioning. MRI scans will be performed over 2 years to determine brain imaging measures that can be used in future studies to distinguish those individuals who are destined to develop schizophrenia from those who do not before the onset of illness.